摘要
背景与目的:检测CXCR4和HER2在乳腺患者的表达水平,观察HER2特异性抗体Herceptin对CXCR4表达和乳腺癌细胞体外转移活性的抑制作用。材料与方法:采用免疫组化法,检测临床不同时期乳腺癌组织CXCR4和HER2的表达水平;采用Western blot检测Herceptin作用后CXCR4蛋白表达,RT-PCR技术检测CXCR4 mRNA的表达;采用趋化实验和粘附实验检测Herceptin对HER2不同表达水平的乳腺癌细胞趋化和粘附活性的影响。结果:CXCR4表达与乳腺癌细胞淋巴结转移状况、乳腺癌组织学分期及HER2的表达呈正相关(P值分别为0.032、0.000和0.015);在高表达HER2的乳腺癌细胞株SKBR3中,Herceptin可下调CXCR4的蛋白及mRNA的表达(P<0.05),并抑制其趋化和粘附活性(P<0.05)。结论:在HER2介导的肿瘤转移中,CXCR4表达上调可能是关键因素。
BACKGROUND AND AIM: We evaluated the expression of CXCR4 and HER2, the inhibition of Herceptin on CXCR4 expression and the in vitro metastatic action in breast cancer cells. MATERIALS AND METHODS: Biomarker expression levels in paraffin-embedded tissue sections of breast cancer were evaluated using immunohistochemical staining. The protein expression of CXCR4 was studied by Western blot and the mRNA expression was by RT-PCR after treatment with Hereeptin . Adhesion and chemotaxis assays were used to evalvate the effect of Herceptin on breast cancer cells with different HER2 expressions. RESULTS: Cytoplasmic CXCR4 was positively correlated with lymph node- positive tumors(P = 0.032)and different stage of breast cancer(P = 0.000)and the expression of HER2(P= 0.015). The protein and mRNA expressions of CXCR4 were decreased after treatment with Herceptin in breast cancer cells with HER2 overexpression(P 〈0.05) and activity of cell adherence to fibronectin(FN) and migration to SDF-1α were inhibited. CONCLUSION: HER2-mediated homing to metastatic organs and upregulation of CXCR4 may be key factors for HER2-mediated breast cancer metastasis.
出处
《癌变.畸变.突变》
CAS
CSCD
2008年第4期303-307,共5页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
安徽省自然科学基金(070413119)
安徽省临床医学应用技术研究计划项目(06B105)
蚌埠市科技计划项目(200617)